(194) Risk Of Cardiovascular Events Among Youths And Young Adults With Concomitant Use Of Atypical Antipsychotics With Antidepressants

Background: Cardiovascular adverse effects of monotherapy with antipsychotic and antidepressant use are reported in youth populations, but limited evidence exists for the risk with concomitant use in youths and young adults.

Objectives: To compare the cardiovascular risk among youth and young adult antidepressant users who initiated a concomitant atypical antipsychotic (AAP) with those who initiated a concomitant antidepressant.

Methods: Using a 25% random sample of the IQVIA PharMetrics® Plus for Academics data, we conducted a retrospective cohort study among youth (3–17 years) and young adults (18-25 years) prescribed an antidepressant from January 2016-November 2022. We calculated the incidence of cardiovascular events among initiators of a concomitant AAP or a concomitant second antidepressant. Covariates were assessed in 180 days prior to initiation of concomitant AAP or concomitant second antidepressant (i.e., index date). The outcome was a composite measure of hospitalization and emergency visits for major (e.g., acute coronary syndrome, heart failure, and ischemic stroke) or less severe adverse cardiac events (e.g., arrhythmia, myocarditis, cardiac arrest, respiratory arrest, and hypertension). We implemented 1:2 propensity score matching (PSM) to estimate the per-protocol effect sizes. In the PSM cohort, a discrete time survival model yielded odd ratios (OR) and 95% confidence intervals (CI) for the risk of cardiovascular events comparing concomitant AAP and antidepressant with two concomitant antidepressants. To adjust for potential unmeasured confounders, we conducted high-dimensional propensity score (HDPS) as a sensitivity analysis.

Results: In our sample of youth and young adults, 1,018 initiated concomitant AAP and 6,372 initiated a concomitant second antidepressant. In the PSM cohort, incidence rate for cardiovascular events was 0.67 per 10,000 person-days for concomitant AAP initiators and 0.40 per 10,000 person-days for concomitant second antidepressant initiators. PSM-adjusted discrete time survival analysis suggested a nonsignificant increased risk of cardiovascular events when comparing initiators of concomitant AAP with initiators of concomitant second antidepressant [OR: 1.68 (95%CI: 0.76, 3.68)]. In the PSM-HDPS adjusted analysis, the OR was 1.07 (95%CI: 0.48, 2.35)].

Conclusions: Despite a non-significant difference between AAP with antidepressants and concomitant use of two antidepressants, the majority of values in the 95% confidence intervals are greater than one. The risk of cardiovascular events associated with concomitant use of AAP with antidepressants warrants further investigation.